Normally, the kidneys filter out excess toxic and waste substances and fluid from the blood. In people with polycystic kidney disease (PKD), the kidneys become enlarged with multiple cysts that interfere with normal kidney function. This can sometimes lead to kidney (renal) failure and the need for dialysis or kidney transplantation.

There are two major forms of PKD: autosomal dominant polycystic kidney disease and autosomal recessive polycystic kidney disease.

●Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease, occurring in approximately 1 in every 400 to 1000 people. Autosomal dominant means that each child of an affected parent has a 50 percent chance of inheriting the disease. In addition, autosomal dominant means that it does not skip generations (ie, if a patient with the disease does not pass it along to one of his or her children, then the disease disappears from that family and grandchildren cannot inherit the disease). However, some patients with ADPKD are not diagnosed during their lifetimes due to very few symptoms. This means that a family member may have the disease without knowing it.

●Autosomal recessive polycystic kidney disease (ARPKD) is uncommon and is typically diagnosed in infancy or in utero, although less severe forms may be diagnosed later in childhood or adolescence. The estimated incidence is approximately 1 in 20,000 people. Autosomal recessive means that the mutated gene must be present in both parents, who, because they carry one abnormal gene, are considered carriers. When both parents are carriers (each having one abnormal and one normal gene), then there is a 25 percent chance that each child will inherit an abnormal gene from both parents and have the disease.

The following is a discussion of ADPKD, the most common polycystic kidney disease.

GENETICS OF AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE

Approximately 85 percent of families with autosomal dominant polycystic kidney disease (ADPKD) have a mutation in the PKD1 gene, located on chromosome 16; these people have PKD1 disease. The remaining 15 percent have a mutation in the PKD2 gene on chromosome 4; this is called PKD2 disease. In some cases, it is not possible to detect which gene is mutated. PKD2 disease is milder; therefore, it often presents later in life and is sometimes not diagnosed at all. Thus, it is likely that more than 15 percent of all people with ADPKD have PKD2 disease.

Kidney failure occurs at an earlier age in PKD1 patients; the average age of end-stage renal disease (that is, needing dialysis or a transplant) is approximately 55 years in PKD1 versus 74 years in PKD2 patients.

In approximately 15 percent of cases, ADPKD occurs in people without a family history of the disease (ie, family members have been evaluated and have no evidence for PKD). This is due to the patient having a new (de novo) genetic mutation that was not present in either parent.

CYST FORMATION

Autosomal dominant polycystic kidney disease (ADPKD) appears to cause abnormal cell growth that leads to cysts on the kidneys. The basic unit of the kidney is the nephron, with each kidney containing approximately one million nephrons (figure 1 and figure 2). Each nephron consists of a glomerulus, which is a collection of very small arteries intermingled among a series of tubules. The glomeruli and tubules work together to filter waste products from the bloodstream and dispose of them in the urine.

In ADPKD, cyst formation begins as an expansion, or ballooning, of a tubule in a small proportion of nephrons. The cyst subsequently enlarges, usually due to fluid secretion into the cyst. The cells making up the cysts multiply, causing the cyst to grow even larger. Cysts may also grow in other organs, including the liver, pancreas, thyroid gland, and/or spleen.

EFFECTS ON THE KIDNEY

Autosomal dominant polycystic kidney disease (ADPKD) often leads to progressive kidney (renal) failure, due primarily to continued enlargement of the cysts and replacement of normal kidney tissue. Other problems involving the kidney can occur, including high blood pressure, kidney infection, blood in the urine (hematuria), and kidney stones. Flank and abdominal pain are also common.

Kidney failure — Kidney (renal) failure severe enough to require dialysis or kidney transplantation is called end-stage renal disease (ESRD). ADPKD rarely leads to ESRD in early childhood; it most commonly occurs in middle age or later in life. The likelihood of requiring dialysis in people with ADPKD is estimated at less than 2 percent in people under age 40, increasing to 50 to 75 percent by age 70 to 75. Not all patients with ADPKD develop kidney failure, particularly those with PKD2. (See "Patient information: Dialysis or kidney transplantation — which is right for me? (Beyond the Basics)".)

Risk factors — The risk of developing kidney failure in ADPKD depends upon a number of factors. As an example, having enlarged kidneys is the most reliable predictor for developing renal failure in patients with ADPKD. In addition, factors that increase the risk of developing kidney failure include being male, having PKD1 disease, having episodes of visible blood or detectable protein in the urine, or having high blood pressure (particularly before age 35). Enlarged kidneys or increased total kidney volume due to a high cyst burden is associated with all of these complications and is the most important risk factor for progression to renal failure.

High blood pressure — High blood pressure is a common feature of ADPKD, occurring in 60 to 70 percent of patients with normal kidney function by the age of 29. Over 90 percent of patients will have high blood pressure by the time they reach end-stage renal failure. Men have higher blood pressures than women, and high blood pressure is associated with bigger kidneys and faster rates of kidney growth. (See "Patient information: High blood pressure in adults (Beyond the Basics)".)

Kidney infection — Approximately 30 to 50 percent of people with ADPKD will have at least one cyst infection during their lifetime. The primary symptoms of a kidney infection in people with ADPKD are fever and flank pain. The infection may be of the kidney or of a cyst. Not all antibiotics work well if the infection is in the cyst. Since it is not easy to tell where the infection is, most physicians will use an oral antibiotic that can penetrate into the cyst cavity. Some people with high fevers or severe symptoms need to be treated with intravenous antibiotics. The duration of treatment for a cyst or kidney infection is typically longer than with a routine kidney infection in someone without ADPKD. (See "Patient information: Urinary tract infections in adolescents and adults (Beyond the Basics)".)

Blood in the urine — Hematuria (blood in the urine) occurs in 35 to 50 percent of people with ADPKD and may be the first sign of the disease. With hematuria, the urine may be a pink or red color. Repeated episodes of hematuria are common. Hematuria is associated with increased kidney size and a faster rate of kidney growth. (See "Patient information: Blood in the urine (hematuria) in adults (Beyond the Basics)".)

Hematuria is usually caused by bleeding into a cyst that communicates with the urinary tract and bladder. This can occur as a result of strenuous activity, and bleeding can cause pain in the side of the low back (called flank pain). Patients with ADPKD can also develop kidney stones, which can cause hematuria and flank pain.

Hematuria related to bleeding cysts generally stops within two to seven days. The usual treatment includes bed rest and increasing fluids until the bleeding stops. If bleeding does not stop with bed rest and increased fluids, a procedure to stop the bleeding may be required. Bleeding into a cyst that does not communicate with the urinary system may not produce visible blood; in this setting, patients typically have localized flank pain and, in some cases, a low-grade fever.

Kidney stones — Kidney stones occur in up to 25 percent of people with ADPKD. Kidney stones may cause pain, or sometimes they can block the flow of urine without symptoms.

Treating kidney stones that block urine flow is extremely important in patients with ADPKD. If the blockage is not relieved, the function in that kidney may be lost. Relieving the blockage may require the help of a urologist. The cysts make it harder to surgically remove the stone or use shock waves to break up the stone (extracorporeal shock-wave lithotripsy [ESWL]). (See "Patient information: Kidney stones in adults (Beyond the Basics)".)

Flank and abdominal pain — Pain is the most common feature of ADPKD. People with ADPKD often develop flank and abdominal pain that is not related to infection, bleeding into a cyst, or a kidney stone. The pain is often dull and persistent, and is thought to be caused by stretching of the wall of a cyst or pressure on other organs when the kidneys and/or liver are very large. This is the most common symptom in ADPKD patients. In contrast, pain that begins suddenly is more likely to be caused by bleeding into or infection of a cyst, twisting of the kidney, or a kidney stone.

No specific treatment is required in most people with dull or persistent flank and abdominal pain; pain medications such as acetaminophen are often recommended. The use of nonsteroidal antiinflammatory drugs (NSAIDs), such as ibuprofen or naproxen, is not recommended, although people with ADPKD may, on occasion, benefit from these medications and should speak to their healthcare provider about the risks and benefits of NSAIDs before using them. NSAIDs are not recommended for patients with ADPKD when kidney function is reduced or when they need to be used on a long-term basis to treat chronic pain basis.

Some people have persistent pain that is severe enough to limit their daily activities. Severe pain is usually evaluated with renal imaging to see if a large cyst is present in the area of pain. If so, a needle through the skin can be used for drainage of the cyst. This needs to be done with appropriate imaging and a radiologist who is trained in this type of technique. Most people have significant relief of pain after drainage. However, pain can recur, and surgery is sometimes required to relieve chronic pain that interferes with quality of life.

ASSOCIATION CONDITIONS OUTSIDE OF THE KIDNEY

A variety of conditions outside the kidney can occur in people with autosomal dominant polycystic kidney disease (ADPKD). These conditions can involve a number of systems, including the liver, vascular system, and the connective tissue.

Intracranial aneurysm — The most serious possible complication of PKD is a cerebral or brain aneurysm (a bulging blood vessel due to weakening of the blood vessel wall). Aneurysms can rupture, causing bleeding into the brain (subarachnoid hemorrhage). If not treated before the aneurysm ruptures, this can lead to irreversible brain damage or death. Aneurysm rupture occurs most often in people with larger aneurysms (>10 mm). The most common symptom of subarachnoid hemorrhage is a severe headache that begins suddenly, often with a pop, frequently with nausea and vomiting. (See "Patient information: Hemorrhagic stroke treatment (Beyond the Basics)".)

Approximately 3 to 7 percent of young adults with ADPKD may have brain aneurysms, and the frequency increases to 12 to 15 percent if someone else in the patient’s family has had an intracranial aneurysm. Compared with the general population, the risk of developing an aneurysm in ADPKD is approximately fivefold greater. People with a first-degree relative with a history of intracranial aneurysm or subarachnoid hemorrhage are at the highest risk of forming an aneurysm.

Early detection (before symptoms occur) of intracranial aneurysms is recommended in people who are at high risk. Screening (looking for an aneurysm before it ruptures) is generally performed with magnetic resonance angiography (MRA) or, if not available, a computed tomography (CT) scan.

At present, routine screening is recommended only for high-risk patients, such as those with a previous rupture; a positive family history of a brain hemorrhage or stroke; warning symptoms (eg, unusual headaches); or a person with a high-risk occupation (eg, airline pilot), in whom a loss of consciousness would place the patient or others at extreme risk.

Liver cysts — Liver cysts occur commonly in people with ADPKD. More than 85 percent of patients will have liver cysts by age 30.

Liver cysts become larger and more numerous as patients age. In addition, women have larger liver cysts than men, particularly women who have had multiple pregnancies or who have taken oral contraceptive pills or hormone replacement therapy for prolonged periods of time.

Most people with liver cysts have no symptoms and have normal or near-normal liver function. However, some people develop abdominal fullness, early satiety, difficulty breathing, or, less commonly, pain (which may require drainage of the cyst, if it is persistent and severe) and/or cyst infection (which requires antibiotic therapy and, in some cases, drainage). Replacing the liver by a liver transplant may rarely be needed in the most severe cases.

Heart valve disease — Abnormalities of the heart valves are detected in up to 25 percent of patients with ADPKD. Most patients with heart valve disease have no symptoms and require no treatment. However, in very rare cases, the valve disease may progress over time and become severe enough to require valve replacement. Some patients with valve disease (mitral valve prolapse) may present with palpitations and may need specific medications (beta blockers).

Abdominal wall hernias — A hernia is an area of weakness in a muscle. The area may protrude if the organs behind the muscle press against the area of weakness, especially as a person increases the pressure in their abdomen (such as during a cough or while carrying a heavy package). Abdominal wall hernias are relatively frequent, affecting approximately 45 percent of people with ADPKD. Abdominal wall hernias are usually located on the midline just above the belly button (ventral) or in the groin (inguinal) areas.

Surgery is the best treatment for abdominal wall hernias that cause pain, but not all hernias require surgical repair. Small hernias may be monitored over time.

POLYCYSTIC KIDNEY DISEASE DIAGNOSIS

It is usually easy to diagnose autosomal dominant polycystic kidney disease (ADPKD) in people who develop flank or abdominal pain and in those who have a family history of ADPKD. An imaging study, such as an ultrasound, is recommended as the first diagnostic test and may reveal multiple cysts on both kidneys. Kidneys are usually enlarged, but may be of normal size in the early stages. Cysts may also be seen in the liver, pancreas, and spleen.

In people without a family history, ADPKD may be more difficult to diagnose. The diagnosis of PKD may first be suspected based on an imaging test, such as an ultrasound, performed for some other reason. The family history may be negative either because family members developed symptoms at a later age and died of other causes before ADPKD was diagnosed, or because a new mutation has occurred (which is the case in 15 percent of patients with ADPKD). If the family history is negative, the diagnosis of ADPKD can be made using information on the number of cysts present in the kidneys in relation to the patient’s age (as described above), and the presence of other clinical findings (such as liver cysts). Rarely, in cases where the imaging diagnosis is not straightforward, genetic testing would need to be performed.

POLYCYSTIC KIDNEY DISEASE TREATMENT

Autosomal dominant polycystic kidney disease (ADPKD) leads to kidney failure due to continued enlargement of the cysts in the majority of patients, typically by the sixth decade of life. Treatment focuses on slowing the progression of kidney failure and treating the associated features of the disease, such as kidney infections or kidney stones and flank or abdominal pain.

High blood pressure — Treating high blood pressure can have a dual benefit in people with PKD because it can help prevent cardiovascular disease and also reduce the likelihood of developing kidney failure.

Dietary protein restriction — There are conflicting findings on the benefit of a low-protein diet in people with ADPKD. Given the limited evidence of benefit, we do not recommend restricting protein intake below 0.8 g/kg of body weight per day. In this example, a 180 pound (82 kg) man would need approximately 66 grams of protein per day.

People with ADPKD who require dialysis are usually treated with hemodialysis. People with ADPKD who have hemodialysis appear to survive longer than people with other types of ESRD.

Peritoneal dialysis, a form of dialysis that involves infusing fluid into the abdomen and then draining the fluid, is less commonly performed due to the presence of the enlarged kidneys, but can be considered on an individual basis. (See "Patient information: Hemodialysis (Beyond the Basics)".)

The prognosis after kidney transplantation is usually excellent.

POLYCYSTIC KIDNEY DISEASE SCREENING

Screening tests are available to relatives of a person with autosomal dominant polycystic kidney disease (ADPKD). The decision to have a screening test for ADPKD should be discussed with an experienced healthcare provider and should include a full discussion of the potential risks and benefits.

Screening in children — The chance of a child being affected by ADPKD when one parent is affected is one in two (50 percent chance). Although a child of a person with ADPKD can be screened for the disease before symptoms develop, screening is not usually recommended during childhood unless the child has signs or symptoms of the disease. Affected children may not yet have cysts that are visible by ultrasound; even if cysts were seen, learning of the diagnosis during childhood would not change the child's medical treatment, but could potentially cause the child to worry. However, children with an affected parent should see a physician regularly and have their blood pressure monitored and a urinalysis performed. Children should also be followed for kidney infections, blood in the urine, kidney stones, and the presence of hernias.

Screening for polycystic kidney disease in adults — An adult with a family history of PKD who has no symptoms may consider being screened for the disease. It is important to realize that, at present, there are no curative or preventative treatments for ADPKD. However, a number of novel treatments are being tested including increased fluid intake, which may have a beneficial effect on the rate of cyst growth and, therefore, kidney size. Importantly, being diagnosed with PKD could potentially affect a person's ability to obtain life insurance. As in children, monitoring for high blood pressure should be performed regularly in adults at risk of having ADPKD.

Ultrasound — When screening is performed, an ultrasound of the kidneys is the most commonly used test. Imaging tests such as ultrasound can be used to screen for ADPKD. The following are ultrasound criteria used to diagnose ADPKD when it is unknown whether the affected parent has PKD1 or PKD2:

●In patients 15 to 39 years of age, at least three cysts (in one or two kidneys) must be seen with ultrasound

●In patients aged 40 to 59, at least two cysts must be seen in each kidney with ultrasound

●In patients over age 60, four or more cysts must be seen in each kidney with ultrasound

In someone older than 40 years, a negative ultrasound usually means that the person does not have ADPKD.

Sometimes, the affected parent is known to have either PKD1 or PKD2. If the parent has PKD2, then a negative imaging study (ie, no cysts in the kidneys) rules out the diagnosis if the person is older than 40 years. If the parent has PKD1, then a negative imaging study rules out the diagnosis if the person is older than 30 years.

As an example, assume a 35-year-old man has a parent with ADPKD, but it is not known whether the parent has PKD1 or PKD2. He undergoes screening ultrasound, which is normal. The normal ultrasound means that he does not have PKD1, but he could still have PKD2 since PKD2 is a more mild disease that may produce cysts later in life. However, people with PKD2 have a lower risk of kidney failure, compared with people who have PKD1, and typically develop kidney failure more than 20 years later than patients with PKD1. This news may be reassuring to some people.

Genetic testing — Genetic tests can also be done to screen for PKD1 or PKD2 mutations, although the use of genetic tests is limited by their cost and the test's inability to make a diagnosis in 15 percent of cases. Genetic tests may be used for:

●A young adult with a family history of ADPKD and a negative ultrasound who is a potential kidney donor

●A person whose ADPKD diagnosis is not certain based upon imaging tests

●A person younger than 30 years of age with a family history of ADPKD and a negative ultrasound who is planning to start a family

Cyst formation in ADPKD may begin in the fetus. However, the disease does not usually cause symptoms in young children. Genetic testing can be done during pregnancy to determine if the baby is affected, although it is not recommended for several important reasons:

●The test may fail to identify ADPKD when it is present

●Some people with gene mutations will never develop symptoms of ADPKD

Special case of pre-implantation screening — For families who are considering in vitro fertilization (IVF) procedures, there is a possibility of screening the eggs to identify those that are free of ADPKD mutation prior to implantation. This requires prior genetic testing of the affected parent and the egg, and comparing them to each other so that a healthy egg can be identified and implanted in the mother’s uterus. Additional cost and time is usually needed for this type of testing, and the chances of having an affected child does not completely go away (5 to 10 percent chance of false-negative testing).

WHERE TO GET MORE INFORMATION

Your healthcare provider is the best source of information for questions and concerns related to your medical problem.

This article will be updated as needed on our website (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for healthcare professionals, are also available. Some of the most relevant are listed below.

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Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.

Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.